Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors

Abstract

Methods, compositions and articles of manufacture for contributing to the treatment of a solid cancerous tumor are disclosed. The methods, compositions and articles of manufacture can utilize an endothelin B agonist (ETB) to enhance the delivery of a chemotherapeutic agent to a solid tumor in mammals, including humans.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 691,915 filed Oct. 23, 2003 which claims the benefit of U.S. provisional patent application No. 60 / 420,960, filed Oct. 24, 2002, U.S. provisional patent application No. 60 / 655,656, U.S. provisional patent application No. 60 / 655,654, and U.S. provisional patent application No. 60 / 655,643 all three filed on Feb. 22, 2005, the entire disclosure of which is incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to methods, compositions and articles of manufacture for contributing to the treatment of solid tumors, such as breast tumors, in a mammal, through administration of an endothelin agonist and a chemotherapeutic agent. BACKGROUND OF THE INVENTION [0003] Breast cancer incidence has increased substantially in the last 10 years, and is the single leading cause of death for women ages 40-49 years in the United States. Suc...

AI Technical Summary

Benefits of technology

[0009] The present invention is directed to the administration of endothelin agonists and a chemotherapeutic agent to an individual in need thereof to contribute to the treatment of a solid tumor. In particular, tumors have distinctive vasculature including an increased number of ETB receptors which, when bound, cause vasodilation. Because ETB receptors are vasodilators, an ETB receptor agonist, in combination with a chemotherapeutic agent, is useful in the treatment of a solid tumor, such as those found in breast cancers. The ETB receptor agonist can more effectively deliver chemotherapeutic agents to tumors resulting in enhanced treatment.

[0010] Specifically, one embodiment of the present invention includes a method of contributing to the treatment of a solid tumor comprising intravenously administering to a mammal in need thereof an ETB agonist and a chemotherapeutic agent, wherein the ETB agonist selectively increases blood supply to the solid tumor thus increasing the delivery of the chemotherapeutic agent to the solid tumor.

[0012] In another embodiment of the methods of the present invention, the ETB receptor agonist enhances the efficacy of the chemotherapeutic agent.

[0020] In another embodiment of the articles of manufacture of the present invention, when the instructions are followed, the ETB agonist selectively increases blood supply to the solid tumor thus increasing the delivery of the chemotherapeutic agent to the solid tumor.

[0022] In another embodiment of the articles of manufacture of the present invention, the ETB receptor agonist enhances the efficacy of the chemotherapeutic agent.

Problems solved by technology

Successful treatment of solid tumors, including breast cancers, remains an unfulfilled medical goal, despite increased understanding of the molecular biology of tumor cells and the availability of an increased number of potential therapeutic agents.

One problem in the treatment of cancers is that an effective dose of a wide variety of potential chemotherapeutic agents is restricted by these agents' non-selective, highly toxic effect on normal tissues.

As a result, many patients suffer from the side effects of chemotherapy without reaping the benefits of the treatment.

The clinical utility of paclitaxel has been hampered, however, by its dose limiting toxicities including hypersensitivity, neutropenia and peripheral neuropathy.

Without constant nourishment from these developing blood vessels, the tumors become hypoxic and subsequently die.

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